CCMT Seminar Series - Jun 8, 2023

The Raymond G. Perelman Center for Cellular and Molecular Therapeutics presents a seminar series:

Protein Monoaminylation in the Brain: Novel Mechanisms of Neural Development, Plasticity and Disease

Speaker:

Ian Maze, PhD
Howard Hughes Medical Institute Investigator
Professor of Neuroscience and Pharmacological Sciences
Icahn School of Medicine at Mount Sinai

Description of Research:

Monoaminergic neurotransmission in the central nervous system plays a critical role in brain development and function. Alterations in monoamine production/signaling are implicated in the development and treatment of neurological diseases, including substance use disorders, mood syndromes and neurodegeneration. Although vesicular packaging of monoamines is essential for brain function, recent data has demonstrated the presence of non-vesicularized pools of monoamines in the nucleus and soma of monoaminergic neurons. Serotonin – as well as other monoamines – has previously been shown to form covalent bonds with certain cytoplasmic proteins. Our group recently identified histone proteins as robust substrates for monoaminylation in brain. Our data indicate that histone monoaminylations act to alter the binding of histone/DNA modification interacting proteins and play direct roles in monoaminergic neuronal transcription. Furthermore, our data indicate pathophysiological associations between altered levels of H3 monoaminylations and behavioral deficits observed in rodent models of disease. This suggests that monoaminergic dysfunction in brain may result in altered genomic enrichment of histone monoaminylations, thereby potentiating aberrant transcriptional plasticity and neurological impairments. Using a unique combination of chromatin biochemistry, genome-wide and neurobiological approaches, we are characterizing the functions of these histone monoaminylation states, and synaptic protein monoaminylations, in the contexts of normal neural function and in rodent models of human disease which promises to provide transformative insights into the underlying mechanisms of monoamine related brain disorders. 

Host: Naiara Aquizu, PhD

Please email aquizun@chop.edu if you would like to meet with the speaker.